ALTERATIONS OF ALDOSE REDUCTASE ACTIVITY BY INDOLE-3-CARBOXALDEHYDE DERIVATIVES

Abstract

In diabetic conditions, aldose reductase (AR, EC 1.1.1.21) activity is significantly increased in lens, kidney and nerve tissues. Mainly in ocular and neural tissues increased levels of sorbitol is associated with diabetic complications such as retinopathy, nephropathy, neuropahty, cataract formation and also tissue damage via increased reactive oxygen speices. Recently, there are many studies that show the relationship between this enzyme family and cancer. Aldose reductase is important for the pathway and in turn has been a potential target for drug design. Great number of aldose reductase inhibitors (ARIs) are used for prevention or delay of these diabetic complications and cancer. However, effective ARIs which has benefits in diabetic complications are still under investigation. In this study aldose reductase was partially purified from bovine lens and the inhibitory effects of 16 different indol-3-carboxyaldehydederivatives on aldose reductase enzyme activities were examined by kinetic assays. These results suggested that N'-[(5-bromo-1H-indol-3-yl)methylidene]pyridine-4-carbohydrazide showed that the highest inhibitory activity on AR.